Cost analysis of CYP2C19 genetic testing in percutaneous coronary intervention patients
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Discovery of ancestry-specific variants associated with clopidogrel response among Caribbean Hispanics
High on-treatment platelet reactivity (HTPR) with clopidogrel predicts ischemic events in adults with coronary artery disease, and while HTPR varies by ethnicity, no genome-wide association study (GWAS) of clopidogrel response has been conducted in Caribbean Hispanics. This study aimed to identify genetic predictors of HTPR in a cohort of 511 Puerto Rican cardiovascular patients treated with clopidogrel, stratified by P2Y12 reaction units (PRU) into responders and non-responders (HTPR). Local ancestry inference (LAI) and traditional GWAS identified variants in the CYP2C19 region associated with HTPR, primarily in individuals with European ancestry. Three variants (OSBPL10 rs1376606, DERL3 rs5030613, RGS6 rs9323567) showed suggestive significance, and a variant in UNC5C was linked to increased HTPR risk. These findings highlight the unique genetic landscape of Caribbean Hispanics and challenge the significance of CYP2C19*2 in predicting clopidogrel response in patients with high non-European ancestry. Further studies are needed to replicate these results in other diverse cohorts.
Pharmaceutical and clinical implications of proton pump inhibitors with dual antiplatelet therapies: a systematic review
Proton pump inhibitors (PPIs) are frequently co-prescribed with dual antiplatelet therapy (DAPT) agents to mitigate the potential of increased gastrointestinal bleeding associated with antiplatelet therapy. Experimental studies have suggested that certain PPIs, such as omeprazole and esomeprazole, may decrease the antiplatelet effects of P2Y12 inhibitors, especially clopidogrel, and, therefore, may potentiate adverse cardiovascular and cerebrovascular events. Data from randomized controlled trials and observational studies have produced mixed results on the clinical implications of this theory. This comprehensive narrative review aims to provide an in-depth analysis of the interactions between PPIs and dual antiplatelet agents, shedding light on their mechanisms and clinical implications and identifying areas for therapeutic optimization. We also address recent advancements in personalized medicine and the potential role of genetic factors in influencing individual responses to PPIs and antiplatelet drugs to optimize treatment outcomes and minimize adverse effects.
Commentary: Why is genetic testing underutilized worldwide? The case for hereditary breast cancer
It is thirty years since the BRCA1 and BRCA2 genes were discovered and genetic testing for BRCA1 and BRCA2 was introduced. Despite increasing awareness of the genetic basis of cancer and our evolving knowledge of effective means of prevention, screening, and treatment for hereditary breast and ovarian cancers, genetic testing is underutilized, and most mutation carriers remain unidentified. In this commentary, we explore possible reasons for why this might be so. Our focus is on factors that may influence or deter a patient from pursuing testing, rather than discussing the implications of receiving a positive test result. Issues of concern include an inadequate number of genetic counselors, restrictive (and conflicting) eligibility criteria for testing, the cost of the test, health insurance coverage, fear of future insurance discrimination, privacy issues, lack of familiarity with the testing process in primary care and gaps in both patient and provider knowledge about the impact and the value of testing. We discuss how these factors may lead to the underutilization of genetic testing in North America and throughout the world and discuss alternative models of genetic healthcare delivery. We have invited leaders in cancer genetic from around the world to tell us what they think are the barriers to testing in their host countries.
Enhancing children’s numeracy and executive functions via their explicit integration
Executive functions (EF) are crucial to regulating learning and are predictors of emerging mathematics. However, interventions that leverage EF to improve mathematics remain poorly understood. 193 four-year-olds (mean age = 3 years; 11 months pre-intervention; 111 female, 69% White) were assessed 5 months apart, with 103 children randomised to an integrated EF and mathematics intervention. Our pre-registered hypotheses proposed that the intervention would improve mathematics more than practice as usual. Multi-level modelling and network analyses were applied to the data. The intervention group improved more than the control group in overall numeracy, even when controlling for differences across settings in EF and mathematics-enhancing practices. EF and mathematics measures showed greater interconnectedness post-intervention. In addition, disadvantaged children in the intervention group made greater gains than in the control group. Our findings emphasise the need to consider EFs in their integration with co-developing functions, and in their educational and socio-economic context.
Intravascular ICG-enhanced NIRF-IVUS imaging to assess progressive atherosclerotic lesions in excised human coronary arteries
Indocyanine green (ICG)-enhanced intravascular near-infrared fluorescence (NIRF) imaging enhances the information obtained with intravascular ultrasound (IVUS) by visualizing pathobiological characteristics of atherosclerotic plaques. To advance our understanding of this hybrid method, we aimed to assess the potential of NIRF-IVUS to identify different stages of atheroma progression by characterizing ICG uptake in human pathological specimens. After excision, 15 human coronary specimens from 13 adult patients were ICG-perfused and imaged with NIRF-IVUS. All specimens were then histopathologically and immunohistochemically assessed. NIRF-IVUS imaging revealed colocalization of ICG-deposition to plaque areas of lipid accumulation, endothelial disruption, neovascularization and inflammation. Moreover, ICG concentrations were significantly higher in advanced coronary artery disease stages (p < 0.05) and correlated significantly to plaque macrophage burden (r = 0.67). Current intravascular methods fail to detect plaque biology. Thus, we demonstrate how human coronary atheroma stage can be assessed based on pathobiological characteristics uniquely captured by ICG-enhanced intravascular NIRF.
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